Cancer as an emergent phenomenon in systems radiation biology

Abstract

Radiation-induced DNA damage elicits dramatic cell signaling transitions, some of which are directed towards deciding the fate of that particular cell, while others lead to signaling to other cells. Each irradiated cell type and tissue has a characteristic pattern of radiation-induced gene expression, distinct from that of the unirradiated tissue and different from that of other irradiated tissues. It is the sum of such events, highly modulated by genotype that sometimes leads to cancer. The challenge is to determine as to which of these phenomena have persistent effect that should be incorporated into models of how radiation increases the risk of developing cancer. The application of systems biology to radiation effects may help to identify which biological responses are significant players in radiation carcinogenesis. In contrast to the radiation biology paradigm that focuses on genomic changes, systems biology seeks to integrate responses at multiple scales (e.g. molecular, cellular, organ, and organism). A key property of a system is that some phenomenon emerges as a property of the system rather than of the parts. Here, the idea that cancer in an organism can be considered as an emergent phenomenon of a perturbed system is discussed. Given the current research goal to determine the consequences of high and low radiation exposures, broadening the scope of radiation studies to include systems biology concepts should benefit risk modeling of radiation carcinogenesis.